Breast enlargement (gynecomastia) in adolescent males is a common phenomenon. Several methods of treatment have been tried. Treatment with the androgenic hormone testosterone has actually caused increased breast size (H. E. Carlson, Gynecomastia, 303 New Eng J. Med. 795-799 (1980)), I.robably because testosterone is converted to the female sex hormone estradiol in vivo by the aromatase enzyme.
In another study, treatment was attempted with an alcoholic solution of Dihydrotestosterone (DHT) applied to the skin. J. M. Kuhn, R. Roca, M. H. Landot, M. Riev, J. P. Luton, Bricase, Studies in the Treatment of Idiopathic Gynaecomastia With Percutaneous Dihydrotestosterone, 520 Clinical Endocrinology 19:513 (1983). While in a majority of patients this was successful and systemic absorption: of DHT was indicated by elevations in its plasma levels, in about 1/5 of the subjects absorption was poor and there was no benefit. Also, in another 1/3 of the subjects, breast regression was incomplete. Another disadvantage of this technique is that the solution must be applied three to four times daily to be effective. This is inconvenient and esthetically objectionable.
It seems that for best results, the gonadotropins--Follicle Stimulating Hormone (FSH) and Leutinizing Hormone (LH)--should be suppressed, for they act on the testes to cause increased testosterone production which (as noted above) is believed to be converted to estradiol in those with gynecomastia. There is considerable dispute as to whether DHT causes suppression of LH or FSH, though suppression of LH alone has been noted in one study. R. J. Santen, Is Aromatization of Testosterone to Estradiol Required for Inhibition of Luetinizing Hormone Secretion in Man?56 J. Clin. Invest. 1555. It seems otherwise clear, however, that long term suppression of LH or FSH can only be achieved through an inhibitor which itself remains in circulation for extended periods. Oral DHT is unsuitable as it is destroyed before reaching the circulatory system. If administered parenterally it has a very short half-life, and, as noted above, topical administration of solution is also effective only for a short time.
Dihydrotestosterone propionate has also been tried. C. Faiman, J. P. Winter, The Control of Gonadotropin Secretion in Complete Testicular Feminization, 39 J. Clin. Endocrinol. Metab. 631-637. However, it has only a one-to three day duration of action and was not effective in gonadotropin suppression. Id.
Insofar as insufficiency of androgenic hormones is treated the same way as gynecomastia--i.e., it is treated by an increase in systemic DHT levels--a thing effective in increasing systemic androgen levels should also function well to treat this syndrome. Moreover, a thing causing suppression of gonadotropins could be effective as a male contraceptive. LH suppression decreases intratesticular androgen levels due to decreased Leydig cell activity. This reduced cellular activity, especially in conjunction with FSH suppression, can significantly reduce or even terminate germ cell proliferation and sperm production. Although previous studies using esterified or unesterified DHT had failed to demonstrate FSH suppression, dihydrotestosterone heptanoate (DHT hep) would probably be suited for this use and all the others noted above.